Hydrogen Peroxide → HCID 59553540, compound

HRID 1170943Notes

Reaction equation

HRID 1170943 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([NH2:24])[CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C[O:26][C:27]1[CH:28]=[C:29]([CH:35]([NH:48]S(C(C)(C)C)=O)CCC2C=CC(C(F)(F)F)=CC=2)[CH:30]=[CH:31][C:32]=1OC.[N:55]1C=CC=C(C=O)C=1.C[Si](C#N)(C)C.C(=O)([O-])[O-].[K+].[K+].OO.[H][H].[BH4-].[Na+]>C1COCC1.CS(C)=O.CO.[Pd].[I-].[Zn+2].[I-].C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([NH:24][CH:28]([C:29]2[CH:35]=[N:48][CH:32]=[CH:31][CH:30]=2)[C:27]([NH2:55])=[O:26])[CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:22])([F:23])[F:21])=[CH:16][CH:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

15

Reactant 8

HCID 784Hydrogen Peroxide2×HCID 103713-PyridinecarboxaldehydeHCID 11430Potassium CarbonateHCID 82115Trimethylsilyl cyanideHCID 4311764Sodium borohydrideHCID 68765446HCID 68765446, compoundHCID 69040547HCID 69040547, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 59553540HCID 59553540, compound

Reagents, catalysts & solvents 6

HCID 23938PalladiumCatalystHCID 9883512zinc(II)iodideCatalystHCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of rac 1-(3,4-dimethoxy-phenyl)-3-(4-trifluoromethyl-phenyl)-propylamine (accessed according to the procedure described for example 126 and 127, step 2 from 2-methyl-propane-2-sulfinic acid [1-(3,4-dimethoxy-phenyl)-3-(4-trifluoromethyl-phenyl)-propyl]-amide, 213 mg, 0.63 mmol) in THF (2 mL) was added 3-pyridinecarboxaldehyde (71 μl, 0.75 mmol), trimethylsilyl cyanide (118 μl, 0.94 mmol) and a catalytic amount of zinc iodide. The solution was stirred for 3 h at ambient temperature before it was diluted with DMSO (0.5 mL) and potassium carbonate (35 mg, 0.25 mmol) and hydrogen peroxide (35% in water, 82 μl, 0.94 mmol) were added. After stirring for 18 h at ambient temperature further hydrogen peroxide (35% in water, 41 μl, 0.47 mmol) was added and stirring continued for 3 h. It was diluted with methanol (0.5 mL) and palladium on charcoal 10% (5 mg) and acetic acid (50 μl) were added. Under an hydrogen atmosphere of hydrogen the reaction mixture was stirred for 3 h at ambient temperature. Sodium borohydride (50 mg) was added and the stirring was continued for 1 h. Purification by chromatography (SiO2, heptane:(ethyl acetate:triethylamine=95:5)=50:50 to 0:100) afforded the title compound as a racemic mixture (1:1) of diastereomers (127 mg, 43%) as a white solid. MS m/e: 472.5 [M−H]−

Workup

  1. additionwere added
  2. additionwas added
  3. stirringstirring
  4. waitcontinued for 3 h
  5. additionwere added
  6. waitthe stirring was continued for 1 h
  7. customPurification by chromatography (SiO2, heptane:(ethyl acetate:triethylamine=95:5)=50:50 to 0:100)

Sources & evidence

ORD record
ord-1e816d11c31f4cfa9df8c09e8f60911c
Source dataset
uspto-grants-2010_11
Patent number
US07829563B2

Reaction notes

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